Is RELN p.Ala7Ser (c.19G>T) pathogenic?

RELN p.Ala7Ser (c.19G>T) is classified Uncertain significance in RELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: likely benign (0.0867); Very rare (popmax 0.00425%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RELN p.Ala7Ser (c.19G>T)?

RELN p.Ala7Ser (c.19G>T) is associated with Inborn genetic diseases (ClinVar).

How common is RELN p.Ala7Ser (c.19G>T) in the general population?

RELN p.Ala7Ser (c.19G>T) is very rare (popmax 0.00425%, nfe) (gnomAD).

What do computational predictors say about RELN p.Ala7Ser (c.19G>T)?

AlphaMissense predicts likely benign (score 0.0867) — an in-silico prediction, not a clinical call.

RELN p.Ala7Ser

c.19G>T · VCV3944476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0867 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00425%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0867	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 432 kb · p 0.0016 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00425% European (non-Finnish) · 49/1,153,088 alleles

Filtering AF 0.00325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00293%

Overall 0.00314% 49/1,562,178 alleles · very rare exomes 47/1,413,206 · genomes 2/148,972 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RELN
Protein: p.Ala7Ser
Coding: c.19G>T
MANE Select: NM_005045
Type: single nucleotide variant
Location: chr7:103989338 (GRCh38)
Gene constraint: LOEUF 0.276 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)

Full RELN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RELN p.Ala7= Likely benign ★ same residue
RELN p.Ala1272Val Uncertain significance ★★ ⚠ same condition
RELN p.Ala1651Ser Uncertain significance ★★ same condition
RELN p.Ala1823Glu Uncertain significance ★★ same condition
RELN p.Ala2742Val Uncertain significance ★★ ⚠ same condition
RELN p.Ala2937Thr Uncertain significance ★★ ⚠ same condition
RELN p.Ala787Ser Uncertain significance ★★ same condition
RELN p.Arg1370Gly Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/reln-p-ala7ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown